TY - JOUR
T1 - Asymptomatic CMV infections in long-term renal transplant recipients are associated with the loss of FcR? from LIR-1+ NK cells
AU - Makwana, Nandini
AU - Foley, Bree
AU - Lee, S.
AU - Fernandez, Sonia
AU - Irish, A.B.
AU - Price, P.
PY - 2016/11/1
Y1 - 2016/11/1
N2 - © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, WeinheimWhile it is established that cytomegalovirus (CMV) disease affects NK-cell profiles, the functional consequences of asymptomatic CMV replication are unclear. Here, we characterize NK cells in clinically stable renal transplant recipients (RTRs; n = 48) >2 years after transplantation. RTRs and age-matched controls (n = 32) were stratified by their CMV serostatus and the presence of measurable CMV DNA. CMV antibody or CMV DNA influenced expression of NKG2C, LIR-1, NKp30, NKp46, and FcR?, a signaling adaptor molecule, on CD56dim NK cells. Phenotypic changes ascribed to CMV were clearer in RTRs than in control subjects and affected NK-cell function as assessed by TNF-a and CD107a expression. The most active NK cells were FcR?–LIR-1+NKG2C– and displayed high antibody-dependent cell cytotoxicity responses in the presence of immobilized CMV glycoprotein B reactive antibody. However, perforin levels in supernatants from RTRs with active CMV replication were low. Overall we demonstrate that CMV can be reactivated in symptom-free renal transplant recipients, affecting the phenotypic, and functional profiles of NK cells. Continuous exposure to CMV may maintain and expand NK cells that lack FcR? but express LIR-1.
AB - © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, WeinheimWhile it is established that cytomegalovirus (CMV) disease affects NK-cell profiles, the functional consequences of asymptomatic CMV replication are unclear. Here, we characterize NK cells in clinically stable renal transplant recipients (RTRs; n = 48) >2 years after transplantation. RTRs and age-matched controls (n = 32) were stratified by their CMV serostatus and the presence of measurable CMV DNA. CMV antibody or CMV DNA influenced expression of NKG2C, LIR-1, NKp30, NKp46, and FcR?, a signaling adaptor molecule, on CD56dim NK cells. Phenotypic changes ascribed to CMV were clearer in RTRs than in control subjects and affected NK-cell function as assessed by TNF-a and CD107a expression. The most active NK cells were FcR?–LIR-1+NKG2C– and displayed high antibody-dependent cell cytotoxicity responses in the presence of immobilized CMV glycoprotein B reactive antibody. However, perforin levels in supernatants from RTRs with active CMV replication were low. Overall we demonstrate that CMV can be reactivated in symptom-free renal transplant recipients, affecting the phenotypic, and functional profiles of NK cells. Continuous exposure to CMV may maintain and expand NK cells that lack FcR? but express LIR-1.
U2 - 10.1002/eji.201646422
DO - 10.1002/eji.201646422
M3 - Article
C2 - 27562679
SN - 0014-2980
VL - 46
SP - 2597
EP - 2608
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 11
ER -